Thiophenol-Based Designer Enzymes

New synthetic building blocks for creating artificial (metallo)enzymes Chemical reactions drive many essential processes, but often proceed too slowly to be practical. Catalysts speed up these reactions, and enzymes, which are proteins that act as biocatalysts, do this with great precision and under sustainable conditions. However, their scope is limited because they are built from only twenty natural building blocks. Artificial enzymes overcome this limitation by adding new synthetic building blocks that do not exist in nature. The PhD research of Mathijs Veen focuses on a special class of such building blocks: thiophenols. These small sulfur-containing groups have useful catalytic properties, but can be difficult to use in synthetic chemistry, partly because of their instability. By incorporating them into proteins, their reactivity can be combined with the selectivity of enzymes. Veen first explored how thiophenols can be incorporated into proteins with genetic methods. He then showed that the presence and position of the thiophenol within the protein strongly influences both activity and selectivity in model reactions. The work also demonstrates that thiophenols can anchor metals, such as gold, at precise locations in a protein. This enabled the creation of stable artificial metalloenzymes capable of performing complex reactions, including stereoselective transformations, which had not been achieved before with gold catalysis inside an enzyme.